Subcutaneous administration of drugs and hydration in acute palliative care units: Physician attitudes and beliefs in the United States and Canada.

OBJECTIVES: The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist. METHODS: This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants. RESULTS: Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p = 0.022) and that it was easier to administer (p = 0.02). US physicians felt the intravenous route was more efficient (p = 0.013). SIGNIFICANCE OF RESULTS: The study results suggest that exposure to the subcutaneous route influences a physician's perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

Mastering Midface Injections.

Injectable filler is one of the most common cosmetic procedures performed annually. An aging face shows a characteristic loss of volume in the deep fat pads of the midface. The goal of midfacial rejuvenation with injectable filler is to restore lost volume, with the suborbicularis fat pad and deep medial cheek fat being the most critical areas. Filler can be instilled here with a cannula or needle with successful outcomes. However, this procedure is not without complications if proper technique and underlying anatomy are not respected.

Deep Eutectic Solvents for Subcutaneous Delivery of Protein Therapeutics.

Proteins are among the most common therapeutics for the treatment of diabetes, autoimmune diseases, cancer, and metabolic diseases, among others. Despite their common use, current protein therapies, most of which are injectables, have several limitations. Large proteins such as monoclonal antibodies (mAbs) suffer from poor absorption after subcutaneous injections, thus forcing their administration by intravenous injections. Even small proteins such as insulin suffer from slow pharmacokinetics which poses limitations in effective management of diabetes. Here, a deep eutectic-based delivery strategy is used to offer a generalized approach for improving protein absorption after subcutaneous injections. The lead formulation enhances absorption of mAbs after subcutaneous injections by ≈200%. The same composition also improves systemic absorption of subcutaneously injected insulin faster than Humalog, the current gold-standard of rapid acting insulin. Mechanistic studies reveal that the beneficial effect of deep eutectics on subcutaneous absorption is mediated by their ability to reduce the interactions of proteins with the subcutaneous matrix, especially collagen. Studies also confirm that these deep eutectics are safe for subcutaneous injections. Deep eutectic-based formulations described here open new possibilities for subcutaneous injections of therapeutic proteins.

A Randomized, Evaluator-Blind, Split-Face Study Evaluating the Safety and Efficacy of Calcium Hydroxylapatite for Jawline Augmentation.

INTRODUCTION: Jawline augmentation with calcium hydroxylapatite has not yet been evaluated in a prospective study with a split-face design. This study aims to perform the first randomized controlled, split-face study on the efficacy and safety of calcium hydroxylapatite for jawline augmentation using the needle and cannula technique. OBJECTIVE: To perform the first randomized controlled, split-face study on the efficacy and safety of calcium hydroxylapatite for jawline augmentation using the needle and cannula technique. MATERIALS AND METHODS: This is a single-site, randomized, evaluator-blind trial enrolling a total of 10 healthy subjects with at least Grade 1 (mild) on a 4-point Jawline Scale. One side of the face was randomized to receive 1 to 2 syringes of calcium hydroxylapatite with lidocaine (total of 3 mL) for correction of wrinkles and folds along the jawline using both the cannula and needle method, and a balancing treatment will be performed 1 month later. Blinded investigator and subject evaluations will be performed immediately after treatment and at the 30-, 60-, and 90-day visits. RESULTS: Ten subjects were enrolled and completed the trial. There was a improvement in the degree of wrinkling and skin sagging in the 4-point Jawline Scale, with an average of a 1.3-point improvement in the scale on the day of treatment and at the Day 30 visit, which remained improved greater than baseline after 3 months as graded by blinded investigators. The Clinician Global Aesthetic Improvement Score for the treated side versus control, as assessed by blinded investigators, demonstrated a improvement with a 2.3-point improvement on the 5-point scale, and by the final visit on Day 90, most patients had a much improved appearance from baseline. CONCLUSION: This study demonstrates that calcium hydroxylapatite is effective and safe for restoration and augmentation of the jawline using the unique needle and cannula technique.

Clinical evaluation of large volume subcutaneous injection tissue effects, pain, and acceptability in healthy adults.

Determining feasibility and tolerability of large volume viscous subcutaneous injection may enable optimized, intuitive delivery system design. A translational early feasibility clinical study examined large volume subcutaneous injection viability, tolerability, acceptability, tissue effects and depot location for ~1, 8, and 20 cP injections at volumes up to 10 ml in the abdomen and 5 ml in the thigh in 32 healthy adult subjects. A commercial syringe pump system delivered 192 randomized, constant rate (20 µl/s) injections (6/subject) with in-line injection pressure captured versus time. Deposition location was qualified via ultrasound. Tissue effects and pain tolerability were monitored through 2 hours post-injection with corresponding Likert acceptability questionnaires administered through 72 hours. All injection conditions were feasible and well-tolerated with ≥79.3% favorable subject responses for injection site appearance and sensation immediately post-injection, increasing to ≥96.8% at 24 hours. Mean subject pain measured via 100 mm visual analog scale increased at needle insertion (6.9 mm, SD 10.8), peaked during injection (26.9 mm, SD 21.7) and diminished within 10 minutes post-removal (1.9 mm, SD 4.2). Immediate injection site wheal (90.9%) and erythema (92.6%) formation was observed with progressive although incomplete resolution through 2 hours (44.6% and 11.4% remaining, respectively). Wheal resolution occurred more rapidly at lower viscosities. Most subjects (64.5%) had no preference between abdomen and thigh. Correlations between tissue effects, injection pressure and pain were weak (Pearson's rho ± 0-0.4). The large volume injections tested, 1-20 cP viscosities up to 10 ml in the abdomen and 5 ml in the thigh, are feasible with good subject acceptability and rapid resolution of tissue effects and pain.

Efficacy and Safety of Treatment of Complex Idiopathic Fistula-in-Ano Using Autologous Centrifuged Adipose Tissue Containing Progenitor Cells: A Randomized Controlled Trial.

BACKGROUND: Mesenchymal stem cells derived from adipose tissue have been successfully used to promote sphincter-saving anal fistula healing. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the use of autologous centrifuged adipose tissue in the healing process of cryptoglandular complex anal fistulas. DESIGN: This is a randomized controlled trial. SETTINGS: This study was conducted at a single center. PATIENTS: Patients with complex perianal fistulas not associated with Crohn's disease were included. Rectovaginal fistulas were not included. INTERVENTIONS: Patients were randomly allocated to receive treatment with centrifuged adipose tissue injection (experimental group) and without injection (control group) in combination with fistula surgery. MAIN OUTCOME MEASURES: The primary outcome was defined as the proportion of patients with complete fistula closure at 4 weeks (short-term outcome) and 6 months after surgery (long-term outcome). Healing was defined as when the external opening was closed with no perianal discharge on clinical assessment. The secondary outcome was safety that was evaluated by the analysis of adverse events up to 3 months after surgery. Pelvic MRI was performed at 3 months to assure safety and the accuracy of the clinical determination of healing. Postoperative pain, return to work/daily activities, persistent closure at 6 months, fecal incontinence, and patient satisfaction were evaluated. RESULTS: Fifty-eight patients who received centrifuged adipose tissue injection and 58 patients who did not receive centrifuged adipose tissue injection were included in the safety and efficacy analysis. After 4 weeks, the healing rate was 63.8% in the experimental group compared with 15.5% in the control group (p < 0.001). No major adverse events were recorded. Postoperative anal pain was significantly lower in the injection group. Time taken to return to work/daily activities was significantly shorter in the experimental group (3 days) than in the control group (17 days). At 6 months, persistent closure was similar in the 2 groups (86.2% vs 81%). Fecal Incontinence Score at 6 months after surgery was identical to the preoperative score. Patient satisfaction was high in both groups. LIMITATIONS: The absence of blinding, the lack of correlation between stem cell content, and the clinical outcome were limitations of the study. CONCLUSIONS: Autologous centrifuged adipose tissue injection may represent a safe, efficacious, and inexpensive option for the treatment of complex fistula-in-ano. See Video Abstract at http://links.lww.com/DCR/B607. CLINICAL TRIALS REGISTRATION: URL: https://www.clinicaltrials.gov. Identifier: NCT04326907. EFICACIA Y SEGURIDAD DEL TRATAMIENTO DE LA FSTULA ANAL COMPLEJA IDIOPTICA UTILIZANDO TEJIDO ADIPOSO CENTRIFUGADO AUTLOGO QUE CONTIENE CLULAS PROGENITORAS UN ENSAYO CONTROLADO ALEATORIO: ANTECEDENTES:Las células madre mesenquimales derivadas del tejido adiposo se han utilizado con éxito para promover la curación de la fístula anal con preservación de esfínter.OBJETIVO:El objetivo de este estudio fue evaluar la eficacia y seguridad del uso de tejido adiposo autólogo centrifugado en el proceso de cicatrización de fístulas anales complejas de origen criptoglandular.DISEÑO:Ensayo controlado aleatorio.ENTORNO CLÍNICO:Estudio unicéntrico.PACIENTES:Se incluyeron pacientes con fístulas perianales complejas no asociadas a Enfermedad de Crohn. No se incluyeron las fístulas rectovaginales.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente para recibir tratamiento con inyección de tejido adiposo centrifugado (grupo experimental) y sin inyección (grupo de control) en combinación con cirugía de fístula.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado primario se definió como la proporción de pacientes con cierre completo de la fístula a las 4 semanas (resultado a corto plazo) y 6 meses después de la cirugía (resultado a largo plazo). La curación se definió cuando orificio externo se cerró sin secreción perianal en la valoración clínica. El resultado secundario fue la seguridad que se evaluó mediante el análisis de los eventos adversos (EA) hasta 3 meses después de la cirugía. La resonancia magnética pélvica se realizó a los 3 meses para garantizar la seguridad y la precisión clínica de la curación. Se evaluó el dolor postoperatorio, el regreso al trabajo / actividades diarias, el cierre persistente a los 6 meses, la incontinencia fecal y la satisfacción del paciente.RESULTADOS:Cincuenta y ocho pacientes que recibieron inyección de tejido adiposo centrifugado y 58 pacientes que no recibieron inyección de tejido adiposo centrifugado se incluyeron en el análisis de seguridad y eficacia. Después de 4 semanas, la tasa de curación fue del 63,8% en el grupo experimental en comparación con el 15,5% en el grupo de control (p <0,001). No se registraron eventos adversos importantes. El dolor anal posoperatorio fue significativamente menor en el grupo de inyección. El tiempo necesario para volver al trabajo / actividades diarias fue significativamente menor en el grupo experimental (3 días) con respecto al grupo de control (17 días). A los 6 meses, el cierre persistente fue similar en los dos grupos (86,2% vs 81%). La puntuación de incontinencia fecal a los 6 meses después de la cirugía fue idéntica a la puntuación preoperatoria. La satisfacción del paciente fue muy alta en ambos grupos.LIMITACIONES:Ausencia de cegamiento, falta de correlación entre el contenido de células madre y el resultado clínico.CONCLUSIONES:La inyección de tejido adiposo centrifugado autólogo puede representar una opción segura, eficaz y económica para el tratamiento de la fístula anal compleja.Registro de ensayos clínicos: www.clinicaltrials.gov, identificador NCT04326907; No patrocinado.Consulte Video Resumen en http://links.lww.com/DCR/B607.

Three-Dimensional Computed Tomography of the Detoured Facial Artery: Variations and Implications for Nasojugal Groove Correction.

BACKGROUND: When performing filler injection procedures to the nasojugal groove, there is the risk of iatrogenic damage to the detoured facial artery. OBJECTIVE: To determine the 3-dimensional location of the detoured facial artery. MATERIALS AND METHODS: The branches of the facial arteries from 118 cadaveric hemifaces were scanned using computed tomography and reconstructed using the Mimics software program. RESULTS: Detoured facial arteries were found in 47 of the 118 hemifaces (39.8%). Two main arterial patterns were identified: in Type I (29 of 47 cases), there were both detoured and nasolabial trunks where the facial artery originated, whereas in Type II (18 of 47 cases), there was only a detoured trunk. The detoured trunk originated 32.0 ± 5.3 mm from the midsagittal line, 5.0 ± 2.8 mm from the occlusion plane, and 5.9 ± 3.5 mm below the skin layer; the inflection of the detoured trunk was located 30.0 ± 5.6 mm laterally, 26.2 ± 4.4 mm superiorly, and 5.7 ± 2.6 mm deep. The meeting point with the inferior orbital rim plane was located 17.1 ± 3.4 mm laterally, 43.4 ± 3.1 mm superiorly, and 2.8 ± 1.7 mm deep. CONCLUSION: The 3-dimensional location of the detoured facial artery as reported here will help clinicians to avoid iatrogenic damage when they are performing filler injection procedures.

An Anatomical Guide to the Terminal Facial Artery: Lumen Diameter and Associated Anatomy Relevant to Dermatologic Procedures.

BACKGROUND: Dermal filler injection in the vicinity of the terminal facial artery (FA) can lead to vascular compromise with devastating consequences, including tissue necrosis, blindness, and stroke. OBJECTIVE: The purpose of this study was to examine lumen diameter and other anatomical features of the terminal FA relevant to dermal filler injection. MATERIALS AND METHODS: Eighteen embalmed adult cadavers were dissected along the distribution of the terminal FA. Gross and microscopic measurements were taken at predetermined points in its course. RESULTS: Mean lumen diameter was largest at the midpoint between the oral commissure and the lateral supra-alar crease (0.81 ± 0.36 mm; point P1) and smallest at the midpoint between the lateral supra-alar crease and the medial canthus (0.43 ± 0.23 mm; point P3). Mean cutaneous depth was deepest at the lateral supra-alar crease (5.06 ± 1.84 mm; point P2) and most superficial at the midpoint between the lateral supra-alar crease and the medial canthus (3.13 ± 2.07 mm; point P3). CONCLUSION: The large-caliber lumen diameter of the terminal FA creates the potential for intra-arterial injection with commonly used filler needles and blunt-tipped cannulas at all points in its course in the nasolabial fold and midface.

Self-injectable extended release formulation of Remdesivir (SelfExRem): A potential formulation alternative for COVID-19 treatment.

There has been a growing and evolving research to find a treatment or a prevention against coronavirus 2019 (COVID-19). Though mass vaccination will certainly help in reducing number of COVID-19 patients, an effective therapeutic measure must be available too. Intravenous remdesivir (RDV) was the first drug receiving Food and Drug Administration (FDA) approval for the treatment of COVID-19. However, in a pandemic like COVID-19, it is essential that drug formulations are readily available, affordable and convenient to administer to every patient around the globe. In this study, we have developed a Self-injectable extended release subcutaneous injection of Remdesivir (SelfExRem) for the treatment of COVID-19. As opposed to intravenous injection, extended release subcutaneous injection has the benefits of reducing face-to-face contact, minimizing hospitalization, reducing dosing frequency and reducing overall health care cost. SelfExRem was developed using a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), dissolved in a biocompatible vehicle. Six different batches were formulated using 2 different grades of low molecular weight PLGA and 3 different PLGA concentration. The force of injection of various polymeric solutions through 23-30-gauge needles were analyzed using a TA.XTplus texture analyzer. The time required for injection was evaluated both manually and by using an autoinjector. In vitro release of all the batches were carried out in 1% v/v tween 80 in phosphate buffer saline. The study indicated that SelfExRem developed with15% w/v PLGA(75:25) provided a steady release of drug for 48 h and may be a breakthrough approach for the treatment of COVID-19.

Effectiveness and Safety of Subcutaneous Rituximab for Patients With Gastric MALT Lymphoma: A Case-Control Comparison With Intravenous Rituximab.

INTRODUCTION: Rituximab is a standard treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). We sought to compare the effectiveness and safety of subcutaneous and intravenous rituximab in a retrospective case-control study. PATIENTS AND METHODS: All consecutive patients with GML treated with subcutaneous rituximab between January 2017 and December 2018 were included and compared to 3 matched control patients (based on Ann Arbor classification, presence of t(11;18) translocation, history of treatment, and type of current treatment) treated with intravenous rituximab between January 2000 and December 2018. Patients with t(11;18) translocation were treated with rituximab in combination with chlorambucil; the other patients were treated with rituximab alone. Effectiveness was assessed at week 52, and safety was assessed through weeks 0 to 52 and compared by the chi-square test. RESULTS: Twenty-five patients were included in the subcutaneous rituximab group and 75 in the intravenous group. There was no difference between the groups in complete remission (78% vs. 76%, P = .99) or overall response rates (91% vs. 89%, P = .99) at week 52. Safety profiles were similar in both groups, with a significant decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group. CONCLUSION: In a small case-control study, we did not find any difference in the effectiveness or safety profiles between subcutaneously and intravenously delivered rituximab for the treatment of patients with GML. We found a decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group.

Pain-less injection: principles and pearls.

There has been an exponential growth in the number of dermatologic procedures performed over the past two decades. This surge in procedural volumes is accompanied by increasing utilization of local anesthetics. A proper technique in administering local anesthesia is necessary to minimize pain and promote comfort, as it is often regarded as the most painful part of cutaneous procedures. Pain is a psychophysiological phenomenon that involves attention, cognitive appraisal, and emotion. Sensory feedback and anxiety are two important aspects of pain perception. This article aims to introduce a novel way that minimizes pain and discomfort associated with local anesthetics. It is the authors' experience that painless injection is achievable by keeping syringes/needles out of sight, proceeding with injection without pre-procedure warning, and engaging patients in a conversation or simple tasks.

Anatomic Characteristics and Treatment of the Midcheek Groove by Deep Filling.

BACKGROUND: Because the anatomic mechanisms underlying the formation of the midcheek groove are unclear, treatments to date have resulted in unsatisfactory outcomes. OBJECTIVE: This study investigated the anatomical foundation of the midcheek groove and evaluated appropriate treatment methods. MATERIALS AND METHODS: Six cadaver hemifacial specimens were subjected to gross anatomic dissection and 6 to P45 sheet plastination. Based on the anatomic results, the area under the orbicularis oculi muscle (OOM) was selected for deep filling. Patients were evaluated by measuring 3D depth, regrading, and self-assessment. RESULTS: The medial band was observed to be an important structure of the OOM, with the facial projection overlapping the midcheek groove trace. Two of the 6 P45 specimens were found to have compact fibroelastic bundles (CFBs) between the medial band and the dermis. Deep filling of the area under the OOM significantly reduced the depth of each section in all 34 patients (p < .001). Grades 3 and 4 midcheek grooves were downgraded distinctively. Most subjects expressed satisfaction with outcomes. CONCLUSION: Formation of the midcheek groove is associated with the passage of CFBs. Deep filling of the area under the OOM effectively improves the midcheek grooves.

Current perceptions of 'Brazilian butt lift' (BBL) surgery in the UK: A BAAPS-led survey of BAAPS members.

BACKGROUND: The BAAPS advice against Brazilian butt lift (BBL) surgery in the UK was set in October 2018. A Delphi study conducted by BAAPS highlighted the importance of defining current practice and perceptions amongst UK surgeons, as this is currently unknown. OBJECTIVES: To evaluate BAAPS members' current practice and perceptions around BBL surgery to ensure patient safety and propose better recommendations. METHODS: A BAAPS-commissioned survey was emailed to all BAAPS members through an on-line link. The survey collected quantitative and qualitative information in several domains. RESULTS: This survey received a 44% response rate. Of 102 respondents, 32 surgeons undertook BBL surgery before the BAAPS advice to halt it. There was a wide variation in actual fat volumes injected, and in perceptions of what constituted a small or large volume. Virtually all respondents (96.9%) performed only subcutaneous fat injections. There were differences in fat harvest techniques. The majority (66.7%) felt that BAAPS should maintain its recommendation against undertaking BBL surgery until further data became available. Nearly a quarter of 102 respondents (20.6%) had been treated for BBL complications, the majority as a result of surgical tourism. CONCLUSIONS: The survey provides member-reported perception and experience with regard to BBL surgery in the UK. The demand for BBL surgery and its provision should be reassessed in the UK. This information will be analysed with further national and international data to better define and shape the scope of the safety of BBL surgery in the UK. BAAPS will use such data towards the production of future guidance and support for surgeons and patients.

Efficacy and Safety of 2 Injection Techniques for Hand Biostimulatory Treatment With Diluted Calcium Hydroxylapatite.

BACKGROUND: Calcium hydroxylapatite (CaHA) is effective for dorsal hand rejuvenation. Higher dilutions are used for biostimulation with fewer side effects. OBJECTIVE: To evaluate the efficacy and safety of 2 techniques of diluted CaHA injection for dorsal hand treatment. METHODS: A prospective, evaluator-blinded study was performed to compare (side-to-side) techniques for treating the dorsum of the hands with diluted CaHA: deep fat lamina or subdermal injection. Fifteen women with aging grades between 1 and 3 on the MHGS (Merz hand grading scale) were enrolled and followed up for 24 weeks. The outcomes were a histological analysis of collagen, skin viscoelasticity, high-frequency ultrasound parameters, MHGS score, and the global aesthetic improvement scale (GAIS) score. RESULTS: Improvement in the MHGS and GAIS scores (p < .01) was observed, with no difference between techniques (p > .05). Skin viscoelasticity measures and ultrasonography for dermal parameters improved for both treatments (p < .01). The mean total collagen density increased from the baseline for both techniques (p < .01). Pain during the procedure as well as adverse effects within the follow-up did not differ between treatments (p > .4). The overall satisfaction was 12% greater for the subdermal technique (p < .05). CONCLUSION: Diluted CaHA improves the skin quality of aging hands with a safe profile, without substantial differences between the techniques.

Tomography of the Forehead Arteries and Tailored Filler Injection for Forehead Volumizing and Contouring.

BACKGROUND: The forehead is a challenging area for filler injection because of the risk of serious complications. Anatomy-based filler injection techniques help to avoid severe vascular complications. MATERIALS AND METHODS: Sixty-six cadaver heads were infused with adequate lead oxide contrast through the external carotid arteries, internal carotid arteries, facial artery, and superficial temporal artery. Three-dimensional computed tomography scans were reconstructed using validated algorithms. We measured the length and arc length of "beautiful" foreheads evaluated by 3 skilled surgeons. RESULTS: The frontal branch of the superficial temporal artery (FBSTA) was classified based on the main trunk as follows: Type I FBSTA (89.72%) took a sudden turn (89.56° ± 11.76°) once passing through the temporal crest, whereas Type II FBSTA (10.28%) barely turned (52.26° ± 6.81°) at the temporal crest. A total of 319 arteries passed through the midline in 48 cadaver heads. There were more superficial arteries (292 of 319) than deep arteries (27 of 319). The difference in the length and arc length of the forehead was 19.66 ± 4.35 mm. CONCLUSION: This study introduces an effective technique for forehead filler injection that minimizes the risk of filler injection and improves patient satisfaction.

Alternative Clinical Indications of Botulinum Toxin.

Botulinum toxin type A (BoNTA) is a powerful neurotoxin that inhibits acetylcholine release from presynaptic vesicles. The potency and safety profile of BoNTA grant the toxin vast therapeutic potential. It has been used off-label for a variety of dermatologic conditions. This review aims to analyze published literature regarding the benefits and risks of the off-label use of BoNTA beyond facial lines, including eccrine hidrocystomas, enlarged pores, keloids and hypertrophic scars, hidradenitis suppurativa, hyperhidrosis, masseter muscle hypertrophy, and salivary gland hypertrophy, among others. A MEDLINE search from January 2000 to December 2019 was conducted on the off-label uses of botulinum toxin in dermatology.